The invention relates to infections from viruses in the herpesviridae family, and more particularly relates to treatment of such infections in living subjects. In its most immediate sense, the invention relates to treatment of such infections using certain ribonucleases (RNases), namely ranpirnase (known also by its registered trademark ONCONASE), the '805 variant of ranpirnase described below, and a recombinant variant of Amphinase 2, also described below.
Ranpirnase is an RNase. It is disclosed and claimed in U.S. Pat. No. 5,559,212. It has been tested and found to be cytotoxic to cancer cells because of its enzymatic activity against RNA. The second embodiment disclosed and claimed in U.S. Pat. No. 5,728,805 (hereinafter, the “'805 variant”) is also an RNase, and has likewise been found to be cytotoxic to certain cancer cells. The '805 variant is a close variant of ranpirnase; its amino acid sequence is identical to that of ranpirnase except that it has valine instead of isoleucine at position 11, asparagine instead of aspartic acid at position 20, and arginine instead of serine at position 103. (In the drawings, the '805 variant is referred to as “Val11, Asn20, Arg103-Ranpirnase”.) Amphinase 2 is also an RNase. It is the protein identified as 2325p4 in U.S. Pat. No. 6,239,257 B1 and it too has been found to be cytotoxic to cancer cells. Recombinant Amphinase 2 (“rAmphinase 2”) is similar to Amphinase 2, but has a Met residue at position −1 and lacks glycan moieties that are located in Amphinase 2 at positions 27 and 91. rAmphinase 2 is described in Example 1 of U.S. Pat. No. 7,229,824 B2 and has SEQ ID NO:59.
Human herpesviridae infections include inter alia herpes simplex virus-1 (“HSV-1”), herpes simplex virus-2 (“HSV-2”), human cytomegalovirus (“HCMV”), Epstein-Barr virus (“EBV”), Kaposi's sarcoma (“HHV-8”), roseolovirus-6A (“HHV-6A”), and roseolovirus-6B (“HHV-6B”). These infections are conventionally treated using acyclovir (“ACV”) and ganciclovir (“GCV”), but existing treatments are not satisfactory. Ganciclovir, which is approved for use in e.g. human cytomegalovirus, is toxic and poorly tolerated. Acyclovir is less toxic and less poorly tolerated, but both drugs are insufficiently active. This is of particular concern in the case of human cytomegalovirus, which frequently manifests itself in immune-compromised patients, such as those who have undergone organ or bone marrow transplants. It would be advantageous to provide a method for treating herpesviridae infections that would be less toxic, better tolerated, and more active.
Ranpirnase, the referenced '805 variant, and a rAmphinase 2 have been discovered to be surprisingly active against certain human herpesviridae infections. Ranpirnase is known to be non-toxic and well-tolerated in humans, and the two other RNases are believed to share these qualities. In accordance with the invention, various herpesviridae infections are treated using these RNases by administering them in therapeutically effective amounts.